Drug Interaction Report

ADJUST DOSING INTERVAL: The gastrointestinal absorption of trientine may be decreased in the presence of food, resulting in reduced therapeutic effects.

MANAGEMENT: Trientine should be administered on an empty stomach, at least one hour before or two hours after meals and at least one hour apart from any other food, drug, or milk.

GENERALLY AVOID: Additive hypotensive effects may occur when phosphodiesterase-5 (PDE5) inhibitors such as tadalafil are used with alcohol, as both are mild systemic vasodilators. In clinical pharmacology studies, more subjects administered alcohol at a dose of 0.7 g/kg (equivalent to approximately 6 ounces of 80-proof vodka in an 80-kg male; consumed within 10 minutes in study subjects, providing blood alcohol levels of 0.08%) in combination with tadalafil 10 or 20 mg single doses had clinically significant decreases in blood pressure than with alcohol alone. There were reports of postural dizziness, and orthostatic hypotension was observed in some. When tadalafil 20 mg was administered with alcohol at a lower dose of 0.6 g/kg (equivalent to approximately 4 ounces of 80-proof vodka in an 80-kg male), orthostatic hypotension was not observed, dizziness occurred with similar frequency relative to alcohol alone, and the hypotensive effects of alcohol were not potentiated. Neither tadalafil nor alcohol affected the plasma concentrations of the other.

GENERALLY AVOID: Coadministration with grapefruit juice is likely to increase the plasma concentrations of tadalafil, which is primarily metabolized by CYP450 3A4. However, the interaction has not been studied. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit.

MANAGEMENT: Patients taking tadalafil should avoid consuming large amounts of alcohol (for example, 5 units or more), which may increase the potential for orthostatic signs and symptoms including increase in heart rate, decrease in standing blood pressure, dizziness, and headache. It may also be appropriate to avoid consuming large amounts of grapefruit juice.

GENERALLY AVOID: Concurrent oral administration of mineral supplements or mineral-containing products may block the absorption of trientine, and vice versa. The mechanism is trientine chelation of polyvalent metal ions resulting in a nonabsorbable complex.

MANAGEMENT: In general, mineral supplements or mineral-containing products (e.g., antacids) should not be used in patients treated with trientine. If concomitant use is unavoidable, separation of administration times by at least two hours is advisable.